tbuckley/cabot-search huggingface dataset:
Lack of Benefit of Iron Chelation in Early Parkinson’s Disease
Authors: Douglas Galasko, Tanya Simuni
Journal: New England Journal of Medicine (2022)

There are no treatments that convincingly slow the progression of Parkinson's disease. One avenue of investigation is based on iron deposition in the brain, which occurs with aging but is also implicated in neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis.1 Iron levels are regulated by binding to transferrin and ferritin, and intracellular iron is partitioned in neurons to prevent toxic effects. Ferroptosis refers to iron-dependent toxicity that triggers lipid peroxidation and other oxidative stresses that lead to cell death.2 Furthermore, cellular iron may exacerbate aggregation of α-synuclein, the neuronal protein that forms Lewy body inclusions . . .
Impact of tissue-agnostic approvals for patients with gastrointestinal malignancies
Authors: Deepak Bhamidipati, Vivek Subbiah
Journal: Trends in cancer (2022)

Gastrointestinal (GI) malignancies encompass a broad range of tumors with limited treatment options, particularly for advanced disease. With the development and implementation of next-generation sequencing (NGS) in routine practice, molecular-targeting therapies have been increasingly incorporated into the treatment paradigm for various cancers. Several drugs have achieved tissue-agnostic regulatory approvals, which offer promising biomarker-driven therapy options for patients with advanced GI malignancies. In this review, we focus on the clinical evidence for recent drug approvals for neurotrophic tyrosine receptor kinase (NTRK) fusion, microsatellite instability-high (MSI-H) phenotype, tumor mutation burden-high (TMB-H), BRAF V600E, and rearranged during transfection (RET), in the context of GI malignancies. We also highlight the future landscape of tissue-agnostic targets, such as human epidermal growth factor receptor 2 (HER2)/neu, fibroblast growth factor receptor (FGFR), and neuregulin (NRG)-1.
Clinical Uncertainties of Circulating Tumor DNA in Human Papillomavirus–Related Oropharyngeal Squamous Cell Carcinoma in the Absence of National Comprehensive Cancer Network Guidelines
Authors: Deborah X. Xie, Carmen Kut, Harry Quon, Tanguy Y. Seiwert, Gypsyamber D'Souza, Carole Fakhry
Journal: Journal of Clinical Oncology (2022)
A population-based study of precision health assessments using multi-omics network-derived biological functional modules
Authors: Wei Zhang, Ziyun Wan, Xiaoyu Li, Rui Li, Lihua Luo, Zijun Song, Yu Miao, Zhiming Li, Shiyu Wang, Ying Shan, Yan Li, Bangwei Chen, Hefu Zhen, Yuzhe Sun, Mingyan Fang, Jiahong Ding, Yizhen Yan, Yang Zong, Zhen Wang, Wenwei Zhang, Huanming Yang, Shuang Yang, Jian Wang, Xin Jin, Ru Wang, Peijie Chen, Junxia Min, Yi Zeng, Tao Li, Xun Xu, Chao Nie
Journal: Cell Reports Medicine (2022)

Recent technological advances in multi-omics and bioinformatics provide an opportunity to develop precision health assessments, which require big data and relevant bioinformatic methods. Here we collect multi-omics data from 4,277 individuals. We calculate the correlations between pairwise features from cross-sectional data and then generate 11 biological functional modules (BFMs) in males and 12 BFMs in females using a community detection algorithm. Using the features in the BFM associated with cardiometabolic health, carotid plaques can be predicted accurately in an independent dataset. We developed a model by comparing individual data with the health baseline in BFMs to assess health status (BFM-ash). Then we apply the model to chronic patients and modify the BFM-ash model to assess the effects of consuming grape seed extract as a dietary supplement. Finally, anomalous BFMs are identified for each subject. Our BFMs and BFM-ash model have huge prospects for application in precision health assessment.
Cloned antibodies from patients with HIT provide new clues to HIT pathogenesis
Authors: Wen Zhu, Yongwei Zheng, Mei Yu, Yaling Wu, Jianhui Wei, Lu Zhou, Guoping Fu, Nicholas Schneider, Curtis Jones, Mehraboon Irani, Anand Padmanabhan, Richard Aster, Demin Wang, Renren Wen
Journal: Blood (2022)
Contribution of mutant HSC clones to immature and mature cells in MDS and CMML, and variations with AZA therapy
Authors: Annatina S. Schnegg-Kaufmann, Julie A. I. Thoms, Golam Sarower Bhuyan, Henry R. Hampton, Lachlin Vaughan, Kayleigh Rutherford, Purvi M. Kakadia, Hui Mei Lee, Emma M. V. Johansson, Timothy W. Failes, Greg M. Arndt, Jason Koval, Robert Lindeman, Pauline Warburton, Alba Rodriguez-Meira, Adam J. Mead, Ashwin Unnikrishnan, Sarah Davidson, Mark N. Polizzotto, Mark Hertzberg, Elli Papaemmanuil, Stefan K. Bohlander, Omid R. Faridani, Christopher J. Jolly, Fabio Zanini, John E. Pimanda
Journal: Blood (2022)

Myelodysplastic neoplasms (MDSs) and chronic myelomonocytic leukemia (CMML) are clonal disorders driven by progressively acquired somatic mutations in hematopoietic stem cells (HSCs). Hypomethylating agents (HMAs) can modify the clinical course of MDS and CMML. Clinical improvement does not require eradication of mutated cells and may be related to improved differentiation capacity of mutated HSCs. However, in patients with established disease it is unclear whether (1) HSCs with multiple mutations progress through differentiation with comparable frequency to their less mutated counterparts or (2) improvements in peripheral blood counts following HMA therapy are driven by residual wild-type HSCs or by clones with particular combinations of mutations. To address these questions, the somatic mutations of individual stem cells, progenitors (common myeloid progenitors, granulocyte monocyte progenitors, and megakaryocyte erythroid progenitors), and matched circulating hematopoietic cells (monocytes, neutrophils, and naïve B cells) in MDS and CMML were characterized via high-throughput single-cell genotyping, followed by bulk analysis in immature and mature cells before and after AZA treatment. The mutational burden was similar throughout differentiation, with even the most mutated stem and progenitor clones maintaining their capacity to differentiate to mature cell types in vivo. Increased contributions from productive mutant progenitors appear to underlie improved hematopoiesis in MDS following HMA therapy.
Outcomes of Salvage Surgery for Initially Unresectable Hepatocellular Carcinoma Converted by Transcatheter Arterial Chemoembolization Combined with Lenvatinib plus Anti-PD-1 Antibodies: A Multicenter Retrospective Study
Authors: Jia-Yi Wu, Zhi-Bo Zhang, Jian-Yin Zhou, Jing-Peng Ke, Yan-Nan Bai, Yu-Feng Chen, Jun-Yi Wu, Song-Qiang Zhou, Shuang-Jia Wang, Zhen-Xin Zeng, Yi-Nan Li, Fu-Nan Qiu, Bin Li, Mao-Lin Yan
Journal: Liver Cancer (2022)

The actual rate of conversion surgery and its prognostic advantages remain unclear. This study aimed to assess the outcomes of salvage surgery after conversion therapy with triple therapy (transcatheter arterial chemoembolization [TACE] combined with lenvatinib plus anti-PD-1 antibodies) in patients with initially unresectable hepatocellular carcinoma (uHCC).Patients with initially uHCC who received at least one cycle of first-line triple therapy and salvage surgery at five major cancer centers in China were included. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) rates after salvage surgery. The secondary endpoints were perioperative complications, 90-day mortality, and pathological tumor response.Between June 2018 and December 2021, 70 patients diagnosed with uHCC who underwent triple therapy and salvage surgery were analyzed: 39 with Barcelona Clinic Liver Cancer (BCLC) stage C, 22 with BCLC stage B, and 9 with BCLC stage A disease. The median interval between the start of triple therapy and salvage surgery was 4.3 months (range, 1.7-14.2 months). Pathological complete response and major pathological response were observed in 29 (41.4%) and 59 (84.3%) patients, respectively. There were 2 cases of perioperative mortality (4.3%) and 5 cases of severe perioperative complications (7.1%). With a median follow-up of 12.9 months after surgery (range, 0.3-36.8 months), the median OS and RFS were not reached. The 1- and 2-year OS rates were 97.1% and 94.4%, respectively, and the corresponding RFS rates were 68.9% and 54.4%, respectively.First-line combination of TACE, lenvatinib, and anti-PD-1 antibodies provides a better chance of conversion therapy in patients with initially uHCC. Furthermore, salvage surgery after conversion therapy is effective and safe and has the potential to provide excellent long-term survival benefits.
Freeze‐Casted Keratin Matrix as an Organic Binder to Integrate Hydroxyapatite and BMP2 for Enhanced Cranial Bone Regeneration
Authors: Wan Ting Sow, Yili Wang, Liping Chen, Qiling Lai, Qiong Chen, Linjie Chen, Chunwu Zhang, Huaqiong Li
Journal: Advanced Healthcare Materials (2022)

Abstract An ideal bone regenerative scaffold is expected to possess architectural characteristics that mimic the bone tissue, osteoconductive properties, and osteoinductive functionality. Key challenges to creating a scaffold with these ideal characteristics simultaneously are the selection of appropriate processing methods and biocompatible materials. Herein, human hair keratin is proposed as an organic binder for the simultaneous incorporation of bone's major inorganic component, hydroxyapatite and bone's growth factor, recombinant human bone morphogenetic protein 2 (rhBMP2) to enable both osteoconductive and osteoinductive characteristics in the creation of bone scaffolds. Furthermore, a freeze‐casting method is selected to fabricate this rhBMP2‐incorporated keratin/hydroxyapatite (KHA) scaffold with aligned lamellar pores to guide and promote bone regeneration. The aligned KHA scaffolds display better mechanical properties, sustained rhBMP2 release, good cell compliance, and 3D cellular infiltration. Implantation of KHA scaffolds in vivo reveals that scaffolds with aligned pores effectively accelerate the healing process of bone defects compared to scaffolds with random pores. This work indicates the distinctive potential of freeze‐casted rhBMP‐2 incorporated KHA scaffolds for bone regeneration.
Oxygen administration during surgery and postoperative organ injury: observational cohort study
Authors: David R McIlroy, Matthew S Shotwell, Marcos G Lopez, Michelle T Vaughn, Joanna S Olsen, Cassandra Hennessy, Jonathan P Wanderer, Matthew S Semler, Todd W Rice, Sachin Kheterpal, Frederic T Billings
Journal: BMJ (2022)

Abstract Objective To examine whether supraphysiological oxygen administration during surgery is associated with lower or higher postoperative kidney, heart, and lung injury. Design Observational cohort study. Setting 42 medical centers across the United States participating in the Multicenter Perioperative Outcomes Group data registry. Participants Adult patients undergoing surgical procedures ≥120 minutes’ duration with general anesthesia and endotracheal intubation who were admitted to hospital after surgery between January 2016 and November 2018. Intervention Supraphysiological oxygen administration, defined as the area under the curve of the fraction of inspired oxygen above air (21%) during minutes when the hemoglobin oxygen saturation was greater than 92%. Main outcomes Primary endpoints were acute kidney injury defined using Kidney Disease Improving Global Outcomes criteria, myocardial injury defined as serum troponin &gt;0.04 ng/mL within 72 hours of surgery, and lung injury defined using international classification of diseases hospital discharge diagnosis codes. Results The cohort comprised 350 647 patients with median age 59 years (interquartile range 46-69 years), 180 546 women (51.5%), and median duration of surgery 205 minutes (interquartile range 158-279 minutes). Acute kidney injury was diagnosed in 19 207 of 297 554 patients (6.5%), myocardial injury in 8972 of 320 527 (2.8%), and lung injury in 13 789 of 312 161 (4.4%). The median fraction of inspired oxygen was 54.0% (interquartile range 47.5%-60.0%), and the area under the curve of supraphysiological inspired oxygen was 7951% min (5870-11 107% min), equivalent to an 80% fraction of inspired oxygen throughout a 135 minute procedure, for example. After accounting for baseline covariates and other potential confounding variables, increased oxygen exposure was associated with a higher risk of acute kidney injury, myocardial injury, and lung injury. Patients at the 75th centile for the area under the curve of the fraction of inspired oxygen had 26% greater odds of acute kidney injury (95% confidence interval 22% to 30%), 12% greater odds of myocardial injury (7% to 17%), and 14% greater odds of lung injury (12% to 16%) compared with patients at the 25th centile. Sensitivity analyses evaluating alternative definitions of the exposure, restricting the cohort, and conducting an instrumental variable analysis confirmed these observations. Conclusions Increased supraphysiological oxygen administration during surgery was associated with a higher incidence of kidney, myocardial, and lung injury. Residual confounding of these associations cannot be excluded. Trial registration Open Science Framework osf.io/cfd2m
A rationally designed cancer vaccine based on NIR-II fluorescence image-guided light-triggered remote control of antigen cross-presentation and autophagy
Authors: Aihua Wu, Afeng Yang, Qinli Tong, Guoguang Wei, Sihang Zhang, Sheng Yu, Chen Zhang, Jiaojiao Xu, Wei Lu
Journal: Acta Pharmaceutica Sinica B (2022)

Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000–1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.
No evidence of clinical efficacy of famotidine for the treatment of COVID-19: a systematic review and meta-analysis
Authors: Huzaifa Ahmad Cheema, Arman Shafiee, Mohammad Mobin Teymouri Athar, Abia Shahid, Rehmat Ullah Awan, Ahmed M Afifi, Jaffer Shah, Prasun K Jalal
Journal: Journal of Infection (2022)
Forthcoming Meetings
Journal: Neuro-Oncology (2022)

Journal Article Forthcoming Meetings Get access Neuro-Oncology, Volume 24, Issue 12, December 2022, Page 2222, https://doi.org/10.1093/neuonc/noac240 Published: 28 November 2022 Article history Corrected and typeset: 28 November 2022 Published: 28 November 2022
Outcome measures reported following feminizing genital gender affirmation surgery for transgender women and gender diverse individuals: A systematic review
Authors: Thomas E. Pidgeon, Thomas Franchi, Andre C. Q. Lo, Ginimol Mathew, Heer V. Shah, Despoina Iakovou, Mimi R. Borrelli, Catrin Sohrabi, Tina Rashid
Journal: International Journal of Transgender Health (2022)

Background Feminizing genital gender affirmation surgery (fgGAS) may be an essential adjunct in the care of some transgender women and gender diverse individuals with gender incongruence. However, the comparison of different techniques of fgGAS may be confounded by variable outcome reporting and the use of inconsistent outcomes in the literature. This systematic review provides the most in-depth examination of fgGAS studies to date, and summarizes all reported outcomes, definitions, and the times when outcomes were assessed following these surgical interventions.Aims/Methods: This work intends to quantify the levels of outcome variability and definition heterogeneity in this expanding field and provides guidance on outcome reporting for future study authors. Candidate studies for this systematic review were sourced via an electronic, multi-database literature search. All primary, clinical research studies of fgGAS were included with no date limits. Paired collaborators screened each study for inclusion and performed data extraction to document the outcomes, definitions, and times of outcome assessment following fgGAS.Results After screening 1225 studies, 93 studies proceeded to data extraction, representing 7681 patients. 2621 separate individual outcomes were reported, 857 (32.7%) were defined, and the time of outcome assessment was given for 1856 outcomes (70.8%) but relied on nonspecific ranges of follow-up dates. "Attainment of orgasm", "Neovaginal stenosis", and "Neovaginal depth/length" were among the most commonly reported outcomes. Profound heterogeneity existed in the definitions used for these and for all outcomes reported in general.Discussion The results demonstrate a need for clear outcomes, agreed definitions, and times of outcome assessment following fgGAS in transgender women and gender diverse individuals. The adoption of a consistent set of outcomes and definitions reported by all future studies of fgGAS (a Core Outcome Set) will aid in improving treatment comparisons in this patient group. This review is the first step in that process.
Transcriptional memory of dFOXO activation in youth curtails later-life mortality through chromatin remodeling and Xbp1
Authors: Guillermo Martínez Corrales, Mengjia Li, Tatiana Svermova, Alex Goncalves, Diana Voicu, Adam J. Dobson, Tony D. Southall, Nazif Alic
Journal: Nature Aging (2022)
Appliances Used by Consumers to Prepare Frozen Stuffed Chicken Products — United States, May–July 2022
Authors: Katherine E. Marshall, Michelle Canning, Michael Ablan, Tamara N. Crawford, Misha Robyn
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Frozen stuffed breaded raw chicken products have repeatedly been implicated in Salmonella outbreaks (1). These products are partially cooked to set the breading, often making them appear cooked (2). Despite their appearance, these products need to be cooked to an internal temperature of 165°F (74°C) to ensure that they are safe to eat. Producers began implementing labeling changes in 2006 to more clearly identify these products as raw; many warn against using microwave ovens (microwaves) to prepare them and provide validated cooking instructions solely for conventional ovens (ovens) (3,4). However, outbreaks continued to occur after implementation of these labeling changes (4). To describe the demographic characteristics of persons who prepare frozen stuffed chicken products and which appliances they use to prepare them, data from a May-July 2022 representative panel survey were analyzed. Although most (82.7%) respondents used an oven as one of their cooking methods, more than one half (54.0%) of respondents also used another appliance, including 29.0% who used a microwave. Oven use was lower among respondents with household income <$25,000 (68.9%), and who lived in mobile homes or other portable types of homes (66.5%). Among respondents who reported using microwaves to cook these products, 8% reported using a microwave with ≤750 W of power, which might be insufficient to thoroughly cook such products (1,5,6). Economic and other factors might influence some groups' access to recommended cooking appliances. Companies could consider implementing additional interventions that rely less on labeling and consumer preparation practices and focus on controlling or reducing levels of Salmonella in these products, such as selling them fully cooked, or monitoring and testing Salmonella levels, to ensure safety. These findings highlight challenges consumers might face in preparing frozen stuffed chicken products safely and can guide strategies for regulatory authorities and industry to prevent outbreaks and illnesses associated with them.
Late-Breaking Basic Science Abstracts From the American Heart Association’s Scientific Sessions 2022
Authors: Keshav Gopal, Qutuba Karwi, Seyed Amirhossein Tabatabaei Dakhili, Cory S Wagg, Liyan Zhang, Qiuyu Sun, Christina Saed, Sai Panidarapu, Riccardo Perfetti, Ravichandran Ramasamy, John R Ussher, Gary D Lopaschuk, Univ of Alberta, Edmonton, Canada, APPLIED THERAPEUTICS, New York, NYU Grossman Med Cntr, New York, UNIVERSITY OF ALBERTA, Edmonton, Canada
Journal: Circulation Research (2022)

Introduction: Diabetic cardiomyopathy (DbCM) increases morbidity and mortality in people with type 2 diabetes (T2D).DbCM is associated with increased fibrosis and adverse remodeling.An increase in cardiac fatty acid oxidation rates can contribute to the development of fibrosis in DbCM.Increased cardiac aldose reductase (AR) activity can also contribute to fibrosis and adverse remodeling in DbCM.Hypothesis: AT-001, a potent and selective AR inhibitor, can mitigate DbCM by inhibiting fatty acid oxidation and decreasing fibrosis in DbCM.Methods: DbCM was induced in male C57BL/6J mice by subjecting them to a high-fat diet (60% kcal from lard) for 10-wk with a single intraperitoneal streptozotocin injection (75 mg/kg) at 4-wk.Mice were randomized to receive either vehicle or AT-001 (40 mg/kg/day) via oral gavage for the last 3-wk.Cardiac function, fibrosis, and myocardial fatty acid oxidation rates were assessed via ultrasound echocardiography, histology, and isolated working heart perfusions, respectively.Results: AT-001 treatment significantly improved diastolic dysfunction (a decrease in the E/e' ratio and an increase in the e'/a') with no effect on systolic function in DbCM mice compared to vehicle-treated mice.Concurrently, there was a significant reduction in cardiac fibrosis and left ventricular (LV) hypertrophy (a decrease in LV mass and cardiomyocyte cross-sectional area) in the AT-001-treated compared to the vehicle-treated DbCM mice.Moreover, cardioprotection by AT-001 was associated with reduced cardiac AR activity and a reduction in myocardial fatty acid oxidation rates (550 ± 113 vs 1156 ± 190 nmol/min/g dry wt) in the DbCM mice compared to the vehicle-treated mice.Furthermore, there was a significant increase in cardiac efficiency depicted by similar cardiac work with a decrease in tricarboxylic acid cycle acetyl CoA production in the AT-001-treated compared to the vehicle-treated DbCM mice.Conclusions: AR inhibition with AT-001 attenuates diastolic dysfunction, cardiac fibrosis, and cardiac hypertrophy in a mouse model of DbCM, which may be due to reduced cardiac fatty acid oxidation rates.
Impact of the early phase of COVID-19 on the trends of isolated bacteria in the national database of Japan: an interrupted time-series analysis
Authors: Masaki Kakimoto, Daisuke Miyamori, Keitaro Omori, Tomoki Kobayashi, Kotaro Ikeda, Seiya Kashiyama, Hiroki Ohge, Masanori Ito
Journal: Journal of Infection (2022)